scholarly journals Results of a UK National Cancer Research Institute Phase II study of brentuximab vedotin using a response‐adapted design in the first‐line treatment of patients with classical Hodgkin lymphoma unsuitable for chemotherapy due to age, frailty or comorbidity (BREVITY)

Author(s):  
Adam Gibb ◽  
Sarah J. Pirrie ◽  
Kim Linton ◽  
Victoria Warbey ◽  
Kathryn Paterson ◽  
...  
Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2677-2677
Author(s):  
Naoko Asano ◽  
Tomohiro Kinoshita ◽  
Koichi Ohshima ◽  
Tadashi Yoshino ◽  
Nozomi Niitsu ◽  
...  

Abstract Abstract 2677 Background: Classical Hodgkin lymphoma (CHL), which is characterized by the presence of Hodgkin and Reed Sternberg (H-RS) cells in a background of non-neoplastic inflammatory cells, is divided into four histological subgroups, nodular sclerosis (NSCHL), mixed cellularity (MCCHL), lymphocyte-rich, and lymphocyte depletion. While NSCHL in young adults is characterized by a mediastinal mass and good prognosis, the clinicopathological characteristics of NSCHL in the elderly (NSCHL-e) remain uncertain. Patients and methods: Enrolled patients were diagnosed with CHL between 1986 and 2006 as part of the Hodgkin Lymphoma's Multicenter Study Group. To better characterize NSCHL-e, we compared the clinicopathological profiles of 84 NSCHL-e patients aged 50 or over with 237 NSCHL-y patients aged 49 or younger and 302 with MCCHL. Results: The total of 743 CHL patients consisted of 496 men and 247 women with a median age of 48 years (range, 15– 89 years). The pathological diagnoses were NSCHL in 324 patients (43%) and MCCHL in 303 (41%). NSCHL patients showed a bimodal age distribution, with an initial peak in their 20s and a second small peak in their 60s. We categorized the former as NSCHL-y (49 or younger) and the latter as NSCHL-e (50 and over). NSCHL-e patients were characterized by male predominance and a more advanced clinical stage (53%) than NSCHL-y. Immunophenotypically, H-RS cells had the prototypic immunophenotype of CD15+ CD30+ and Pax5+. NSCHL-e cases showed a significantly higher rate of CD20 (24%) than NSCHL-y (8%, P = 0.001). Furthermore, H-RS cells in 29 of 75 (39%) patients with NSCHL-e were positive for EBV RNA transcripts by in situ hybridization, whereas only 7% of NSCHL-y cases were EBER-positive (P < 0.0001) (Table). Regarding NSCHL-e and MCCHL, no significant difference between these patients was seen in clinical characteristics. Immunophenotypically, NSCHL-e patients showed significantly higher rates for CD3 and TIA-1, while MCCHL patients showed higher EBV positivity (75%). Fifty-five of 63 patients received systemic multi-agent chemotherapy as first-line treatment, consisting of doxorubicin, bleomycin, vinblastine, and dacarbacin (ABVD) in 38 patients; CHOP in 8; C-MOPP in 8; and BEACOPP in 1. Overall, 51 patients responded to first-line treatment, 39 with complete response and 12 with partial response. Disease-specific survival of NSCHL-e was poorer than that of NSCHL-y (P < 0.001) but similar to that of MCCHL (P = 0.43) (Figure). Conclusion: NSCHL-e is characterized by an unfavorable prognosis and different clinicopathological features to NSCHL-y, which is considered as typical NSCHL. A number of cases of NSCHL-e might have been associated with MCCHL, with most being EBV-positive. These results suggest the limitations of current histological subgroupings for CHL. Disclosures: Matsushita: Pfizer CO.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter Co.: Membership on an entity's Board of Directors or advisory committees, Research Funding.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8029-8029 ◽  
Author(s):  
Jean Marc Schiano de Colella ◽  
Simonetta Viviani ◽  
Davide Rapezzi ◽  
CATERINA PATTI ◽  
Lauriane Clement Filliatre ◽  
...  

8029 Background: Hodgkin Lymphoma (HL) treatment in the elderly is a challenge, as standard ABVD is able to cure no more than 60% of the patients (p.). Bendamustine (Be), and Brentuximab Vedotin (BV), are well-tolerated and effective drugs in relapsing HL, but only preliminary data exist in 1st line treatment of the elderly (Evens AM 2018). Methods: HALO is a prospective international multicenter open-label phase I/II study (NCT02467946) to assess the safety and efficacy of Be-BV in advanced-stage elderly HL p. Briefly, BV 1.2 mg/kg on D1, and Be 90 mg/m2 on D1-2 were administered Q3W for 6 cycles. The primary endpoint was the feasibility and the efficacy of Be-BV. Results: Between July 2015 and February 2019, 59/60 p. consecutive enrolled received at least 1 Be-BV cycle, and are valuable for primary endpoint. One p. was excluded because a histological review showing angioimmunoblastic T-Cell Lymphoma. The mean age was 70.32 (62-79), and M/F ratio 41/18. The Ann-Arbor stage was IIB in 12, III in 14 and IV in 33 patients, B-symptoms (y/n) 40/19. IPS was 0-2 in 19 and ≥ 3 in 40 p., P.S. (ECOG) was 0-1 in 53, 2 in 6 p., nonetheless most of them were frail, as ADL was ≥ 6 in 47 (79%) and IADL was ≥ 8 in 42 (71%) p. Most frequent co-morbidities were cardio-vascular disease (45) metabolism disorders (31) prostatic adenoma (11). 163 treatment-related adverse events (WHO 3-4) were recorded: neutropenia and lymphopenia, (134), infections (7), cutaneous reactions (5), liver toxicity (2). No case of grade > 2 peripheral neuropathy was recorded. Out of 59 p., 41 concluded and 18 interrupted the treatment for toxicity (8), progression (5), treatment failure (2), CMV reactivation (3). The latter was recorded in 17 p., 12/17 received valgancyclovir. 4 p. died with CMV viremia. After a mean follow-up of 20.6 (0.3-46.5) months, 37/59 (63%) were in CR, while 22 (37%) have progressed (5) or relapsed (17). The 2-y OS and PFS in ITT analysis were 83% (95% CI 71-96) and 54% (95% CI 41-72) and in PP 89% (95%CI 75-100) and 78% (95%CI 64-96), respectively. 22 p. had a PFS event: 5 progression (2 deaths), 17 relapse (8 deaths). 10 p. died for recurrent HL (5), sepsis (1), secondary malignancy (2), respiratory insufficiency (1) and unknown (1). Conclusions: The Be-BV combination, a novel anthracycline-free regiment for first line treatment of HL in elderly, proved effective in unselected, frail, poor-risk, HL p. aged more than 60 in daily hospital real life. The CMV reactivation is frequent and should be treated with preemptive antiviral therapy upon detection of CMV DNA in plasma. Clinical trial information: NCT02467946 .


Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4786-4786
Author(s):  
Joseph Feliciano ◽  
Kerstin Mueller ◽  
Ellen E Korol ◽  
Zhouqin He ◽  
Niloufer Khan ◽  
...  

Abstract Introduction: The standard of care for previously untreated classical Hodgkin lymphoma (HL) in the United States has been combination chemotherapy with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) alone or with radiotherapy depending on clinical characteristics. Other treatment programs exist, including intensified chemotherapy regimens, and substitution of brentuximab vedotin for bleomycin recently received FDA approval as first-line therapy for advance stage HL. The objective of this study was to understand how specific treatment attributes impact preferences among patients and physicians for choice of first-line treatment of HL. Methods: An online survey including a discrete choice experiment (DCE) was administered both to oncologists who manage patients with HL and to patients diagnosed within HL within the last two years in the United States. Participants were identified via online research panels. The attributes and levels of the hypothetical treatments presented in the DCE were informed by targeted literature review and physician and patient interviews. For physicians, six attributes were included: two-year overall survival (OS); two-year progression free survival (PFS); risk of side effects requiring hospitalization; risk of peripheral neuropathy (PN); risk of pulmonary toxicity; and patient out-of-pocket cost. The patient DCE included four attributes: OS, PFS, risk of PN and risk of pulmonary toxicity. DCE scenarios were developed using a d-efficient design. Participants reviewed 10 scenarios, and selected their preference between two hypothetical treatments. Patients considered themselves when selecting their preference; physicians considered four different advanced HL patient profiles that differed in age (30 or 65 years), smoking status, and the presence of baseline PN. The DCE data were analyzed using a mixed logit model (MXL). The relative importance of each attribute was calculated by determining the differences between the maximum and minimum coefficients of each attribute. These were then normalized and presented as percentages. Results: A total of 200 physicians and 141 patients were included in the analysis. Physicians had a mean of 15 years' experience and 71% practiced in a community setting. Patients had a median age of 35 years (range 19 to 69), 60% were male, and 34% were diagnosed with advanced stage HL. In the DCE, the most important attributes to both patients and physicians were OS and PFS. Based on the coefficients from the MXL model, a 1% increase in OS was more important to both groups than a 1% increase in PFS. The coefficients and level ranges for each attribute were used to calculate preference weights (see methods). Based on preference weights, PFS was the most important attribute for patients, followed by OS, risk of pulmonary toxicity, and risk of PN (Table 1). Compared to male patients, there was a trend for female patients to have a lower preference for a 1% decrease in risk of progression (p=0.077). Patients above the median age of 35 years had a significant preference (p=0.048) for a lower risk of pulmonary toxicity, and a trend for a higher preference for a 1% increase in OS (p=0.059) was observed. OS was also marginally more important to patients diagnosed with advanced stage HL versus those diagnosed in earlier stages. For physicians, preferences for treatment attributes differed based on the patient profile presented. PFS outweighed OS for a healthy 35 year-old patient (Table 2), whereas OS had a higher relative preference weight for a 35 year old smoker and older patients. For smokers, physicians ranked pulmonary toxicity as the most important attribute. Among older patients, side effects requiring hospitalization were more important to physicians' preferences than both OS and PFS. There were no major differences in preferences between academic and community oncologists. Conclusion: Patients are willing to accept treatments with worse short and long-term side effects in exchange for improved OS or PFS. Physicians' treatment preferences are patient-specific, with age and comorbidities impacting both the relative weight of OS and PFS attributes and the importance of pulmonary toxicity and short-term side effects. These results underscore the importance of assessing and sharing patient and physician preferences in creating a treatment plan for the management of newly diagnosed Hodgkin lymphoma. Disclosures Feliciano: Seattle Genetics: Employment, Equity Ownership. Mueller:ICON plc: Employment. Korol:ICON plc: Employment. He:ICON plc: Employment. Matasar:Seattle Genetics: Honoraria.


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